1.
Anticonvulsant agents are commonly used to treat
neuropathic pain conditions because of their effects on voltage- and
ligand-gated channels in central
pain pathways. However, their interaction with
ion channels in peripheral
pain pathways is poorly understood. Therefore, we studied the potential
analgesic effects of commonly used
anticonvulsant agents in peripheral nociception. 2. We injected
anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used
anticonvulsants such as voltage-gated Na+ channel blockers,
phenytoin and
carbamazepine, and voltage-gated Ca2+ channel blockers,
gabapentin and
ethosuximide, induced dose-dependent
analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 microg per 100 microl, respectively. 3. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of
anticonvulsants that elicited local
analgesia. 4. Hill slope coefficients for the tested
anticonvulsants indicate that the dose-response curve was less steep for
gabapentin than for
phenytoin,
carbamazepine and
ethosuximide. 5. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of
anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied
anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful
analgesics.